First Genome-Wide Profiling of Transcription Start Sites in Drosophila melanogaster
µç³µÎÞÂë, IL — May 11, 2009 —
In an international effort, scientists at the Illinois Institute of Technology, together with industrial partners at DNAFORM in Japan, imaGenes in Germany, FASTERIS in Switzerland, and Precision Biomarker Resources in the USA, have for the first time prepared a genome-wide map of Transcription Start Sites (TSS) for the fruit fly Drosophila melanogaster. Drosophila is one of the best-studied model organisms in biology and has greatly contributed to our understanding of genetics, development, physiology, and behavior.
With the increasing availability of genome sequences, research has shifted to transcriptome analysis for a greater understanding of how genomic information is utilized in a regulated manner. Recent data obtained by new Next-Generation Sequencing Methods indicate genome-wide RNA transcription from both DNA strands at unexpectedly high levels with complex overlapping patterns. Of the different approaches to genome and transcriptome analysis, the Cap Analysis Gene Expression (CAGE) Method developed by the RIKEN Omics Center and DNAFORM, in combination with Next-Generation Sequencing, is uniquely placed to identify TSS on a genome-wide level with high accuracy experimentally and the precision required assessing such diverse expression patterns. After major contributions to the RIKEN FANTOM and NIH ENCODE projects, CAGE has now, for the first time, been applied to Drosophila melanogaster. Identifying TSS in Drosophila is a valuable contribution to arguably the best-annotated genome. The availability of genome sequences of 11 additional Drosophila species in combination with CAGE-identified TSS in Drosophila melanogaster promises great insights into evolutionary aspects of gene expression.
We expected the most highly expressed CAGE tags to be linked to well-annotated gene transcripts in Drosophila. However, initial analysis of our data shows only 25% of the highly expressed CAGE tag clusters map close to annotated TSS. CAGE studies of other organisms showed that about half of all genes have alternate promoters and/or transcripts originating within genes and distances upstream. That 75% of our highly expressed CAGE tag clusters are not tightly linked to known TSS even in the well-annotated Drosophila genome suggests that transcription is much more complex than previously thought. Associating CAGE tags with exons and 3' UTRs and linking transcripts to genes at variable distances away on both DNA strands will promise a greater understanding of genome expression in Drosophila. Moreover, less highly expressed CAGE tag clusters point to wider expression of the Drosophila genome than described by the present annotation. Our study has thus potentially identified new promoter sites for known genes and entirely new transcriptional events.
A unique advantage of the Drosophila system is that the worldwide Drosophila research community can rapidly test the implications of our new CAGE results. Molecular, genetic, developmental, and behavioral experiments on genes of particular interest will test the biological importance of newly detected promoter regions and the gene expression they drive. Similarities have been found between flies and humans, and results from Drosophila are expected to drive further advances in other species, including humans.
Founded in 1890, IIT is a Ph.D.-granting university with more than 7,300 students in engineering, sciences, architecture, psychology, design, humanities, business, and law. IIT's interprofessional, technology-focused curriculum is designed to advance knowledge through research and scholarship, cultivate inventions that improve the human condition, and prepare students worldwide for a life of professional achievement, service to society, and individual fulfillment. Visit www.iit.edu.
